You are here

N Engl J Med DOI:10.1056/NEJMoa0804525

Gene expression in fixed tissues and outcome in hepatocellular carcinoma.

Publication TypeJournal Article
Year of Publication2008
AuthorsHoshida, Y, Villanueva, A, Kobayashi, M, Peix, J, Chiang, DY, Camargo, A, Gupta, S, Moore, J, Wrobel, MJ, Lerner, J, Reich, M, Chan, JA, Glickman, JN, Ikeda, K, Hashimoto, M, Watanabe, G, Daidone, MG, Roayaie, S, Schwartz, M, Thung, S, Salvesen, HB, Gabriel, S, Mazzaferro, V, Bruix, J, Friedman, SL, Kumada, H, Llovet, JM, Golub, TR
JournalN Engl J Med
Date Published2008 Nov 06
KeywordsAged, Carcinoma, Hepatocellular, Feasibility Studies, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome-Wide Association Study, Humans, Liver, Liver Neoplasms, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local, Oligonucleotide Array Sequence Analysis, Paraffin Embedding, Polymerase Chain Reaction, Prognosis, Survival Analysis, Tissue Fixation

BACKGROUND: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue.

METHODS: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival.

RESULTS: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04).

CONCLUSIONS: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.


Alternate JournalN. Engl. J. Med.
PubMed ID18923165
PubMed Central IDPMC2963075
Grant List1R01DK076986-01 / DK / NIDDK NIH HHS / United States
5U54 CA112962-03 / CA / NCI NIH HHS / United States
R01 DK037340-14 / DK / NIDDK NIH HHS / United States
R01 DK076986 / DK / NIDDK NIH HHS / United States
DK37340 / DK / NIDDK NIH HHS / United States
R01 DK076986-01 / DK / NIDDK NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
U54 CA112962-03 / CA / NCI NIH HHS / United States
R01 DK037340 / DK / NIDDK NIH HHS / United States